title: Hormone-regulated transcriptomes: lessons learned from estrogen signaling pathways in breast cancer cells.
abstract: Recent rapid advances in next generation sequencing technologies have expanded our understanding of steroid hormone signaling to a genome-wide level. In this review, we discuss the use of a novel genomic approach, global nuclear run-on coupled with massively parallel sequencing (GRO-seq), to explore new facets of the steroid hormone-regulated transcriptome, especially estrogen responses in breast cancer cells. GRO-seq is a high throughput sequencing method adapted from conventional nuclear run-on methodologies, which is used to obtain a map of the position and orientation of all transcriptionally engaged RNA polymerases across the genome with extremely high spatial resolution. GRO-seq, which is an excellent tool for examining transcriptional responses to extracellular stimuli, has been used to comprehensively assay the effects of estrogen signaling on the transcriptome of ERα-positive MCF-7 human breast cancer cells. These studies have revealed new details about estrogen-dependent transcriptional regulation, including effects on transcription by all three RNA polymerases, complex transcriptional dynamics in response to estrogen signaling, and identification novel, unannotated non-coding RNAs. Collectively, these studies have been useful in discerning the molecular logic of the estrogen-regulated mitogenic response.
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, United States. Electronic address: nhah@salk.edu.
authors.forename: Nasun
authors.initials: N
authors.lastname: Hah
authors.affiliation: The Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States.
authors.forename: W Lee
authors.initials: WL
authors.lastname: Kraus
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*
chemical_list: D004967:Estrogens
keywords: 17β-estradiol; Breast cancer cells; ChIP; E2; ERBS; ERα; Estrogen; Estrogen receptor; GRO-seq; HMM; Non-coding RNA; Pol (I, II, III); RNA polymerase (I, II, III); SERM; Transcriptome; chromatin immunoprecipitation; eRNA; enhancer RNA; estrogen receptor alpha; estrogen receptor α binding site; global nuclear run-on and sequencing; hidden Markov model lncRNA, long non-coding RNAs; mRNA; messenger RNA; rRNA; ribosomal RNA; selective estrogen-receptor modulator; tRNA; transfer RNA